While the development of effective single dose vaccines would have major implications for the effectiveness of mass immunization programs, the development of single dose vaccines is fraught with a complex combination of clinical and engineering challenges. Several health organizations have listed the development of single dose vaccines as one of the “grand challenges” of human health worldwide. Even diseases for which effective vaccines exist remain a threat to public health because patient dropout rates (after initial vaccinations) reach as high as 70% in developing countries (Aguado, M. T.; Lambert, P.-H. (1992) Immunobiology 184, 113-125.). Improved vaccine delivery techniques that require only a single dose to confer protective immunity against childhood diseases would help make mass immunization programs successful. For instance, tetanus is responsible for over 700,000 neonatal deaths annually, half of which could be prevented by immunization alone.
Induction of the appropriate immune response is essential to the safety and efficacy of vaccines (Woodland, D. L. (2004) Trends Immunol. 25, 98-104). While traditional alum-based vaccines, incorporating tetanus toxoid (TT) in particular, initiate primarily a T helper type 2 (TH2) response (Singh, M.; O'Hagan, D. T. (2003) Int. J. Parasitology 33, 469-478), a T helper type 1 (TH1) response may be more effective for protection from or treatment of cancers or infections due to intracellular pathogens (Hanes, J., Cleland, J. L., Langer, R. (1997) Adv. Drug Del. Rev. 28, 97-119). However, the mechanisms governing the type of immune response are complex and not completely understood (Sedlik, C., Dériaud, E., Leclerc, C. (1997) Int. Immunol. 9, 91-103). The TH2 (humoral) response, characterized by the activation of B cells that differentiate into plasma cells that secrete antibodies, is effective to neutralize extracellular pathogens and toxins, but not to neutralize intracellular pathogens. The TH1 (cell-mediated) response, involving the activation of interferon-γ producing CD4+ T cells, CD8+ cytotoxic (“killer”) T cells, and macrophages, is effective against intracellular pathogens (Finkelman, F. D.; Urban, J. F. J. (1992) Parasitol. Today 8, 311-314). The ability to purposefully modulate the immune response to more effectively protect the host from a particular pathogen would improve the effectiveness of vaccines in combating many worldwide diseases.
A single-dose vaccine would alleviate problems associated with conventional vaccination programs that have high dropout rates. Also, no currently existing formulation can provide a tunable immune response in a single-dose formulation. Accordingly, there is a need for development of improved technologies or regimen that allow for the development of new single-dose vaccines for intracellular pathogens that require a preferential induction of the TH1 immune response. A need also exists for development of improved technologies or regimen that allow for the development of new single-dose vaccines that induce a balance of both the TH1 and TH2 responses for protection from other conditions such as HIV/AIDS and certain types of cancers.